Antiangiogenic mechanisms of simvastatin in retinal endothelial cells

Yasuaki Hata, Muneki Miura, Ryo Asato, Takeshi Kita, Kumiyo Oba, Shuhei Kawahara, Ryoichi Arita, Ri Ichiro Kohno, Shintaro Nakao, Tatsuro Ishibashi

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Background: While statins have an anti-angiogenic property, their underlying mechanisms are not fully understood. We investigated intracellular mechanisms of simvastatin-mediated reduction in VEGF-induced signalings. Methods: The effects of simvastatin on cell proliferation and viability were evaluated by [3H]-thymidine incorporation in retinal endothelial cells (RECs) and cell counting. The impact of simvastatin on VEGF-induced phosphorylation of p44/42 mitogen-activated protein (MAP) kinase, myosin light chain (MLC), and VEGF-receptor (VEGFR) 2 were examined by Western blotting. Involvement of the mevalonate pathway in VEGF-induced signaling was also examined. Results: Simvastatin (1 and 10 μM) suppressed VEGF-induced RECs proliferation in a concentration-dependent manner, without affecting cell viability. Simvastatin significantly inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream mediators, p44/42 MAP kinase and MLC. Mevalonate completely reversed VEGF-induced VEGFR2 phosphorylation, but only partially reversed the phosphorylation of p44/42 MAP kinase and MLC. Conclusion: These data indicate that simvastatin exerts its anti-angiogenic effects through the reduction of VEGFR2 phosphorylation in RECs at least in part. However, there seems to be both mevalonate-dependent and independent pathway in simvastatin's anti-angiogenic property.

Original languageEnglish
Pages (from-to)667-673
Number of pages7
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Issue number5
Publication statusPublished - 2010

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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